Multiple sclerosis (MS) is a chronic demyelinating disease in which activation of the immune system is thought to play an important role. Recently it has become evident that many factors act both in the nervous and immune systems. Insights int MS may thus be gained by gaining an understanding of the relations and intercommunications between the systems mediated by these factors. We have isolated, cloned and expressed a novel polypeptide factor, neuroleukin (NLK), which possesses both neurotrophic and lymphokine activity. Neuroleukin supports survival in vitro of spinal cord neurons and of that population of dorsal root ganglion neurons that is refractory to nerve growth factor. Neuroleukin is found in muscle, in brain, and in the C6 glioma cell line. Activated T cells also express neuroleukin and B cells respond to it by producing immunoglobulin. We believe that brain astrocytes produce NLK and that in the MS disease process these cells may stimulate T and of B lymphocytes to autoimmune reactivity. We propose three types of experiments to investigate this possibility. The first type of experiments will investigate regulation of neuroleukin production by astrocytes stimulated with immunomodulators including interferon-gamma. The second type of experiment will determine the role of astrocyte-derived NLK in stimulating polyclonal B-cell activation. The third category of experiments will investigate the role of NLK in experimental allergic encephalomyelitis, a model for MS.